Water-Mediated Synthesis of Oxindole-Embedded Chalcone Hybrids: Anticancer Evaluation and Computational Insights

Abstract Objective: This study presents an eco-friendly, aqueous-phase synthesis of a series of oxindole-derived chalcone hybrids with promising anticancer activity. Methods: Molecular docking studies were performed against the ATP-binding site of the RET kinase domain (PDB ID: 6NEC), a validated anticancer target. Molecular dynamics simulations confirmed the stability of the protein-ligand complexes. Results and Discussion: Among the synthesized derivatives, compounds IIId, IIIg, IIIa, and IIIc exhibited notable cytotoxicity against the A549 human lung adenocarcinoma cell line, with IC50 values ranging from 8.85 to 13.87 μM. The compounds demonstrated strong binding affinities, with docking scores ranging from –9.071 to –5.138 kcal/mol. The root-mean-square deviation (RMSD) of the protein backbone remained below 2 Å throughout the 100-ns simulation period. Conclusions: These integrated findings suggest that compound IIId and its structural analogs represent promising lead candidates for further development as anticancer agents.